The present invention relates to a non-radioactive composition useful for labeling red blood cells with radioactive technetium, and its preparation and use. More particularly, it relates to a non-radioactive composition being useful for the efficient attainment of intracorporeal labeling of red blood cells in living bodies with radioactive technetium, and having a high stability, and no material toxicity, and its preparation and use.
Radioactive substances which are not taken into any organ when administered into blood vessels and which remain in the blood circulation system are useful for obtaining medically valuable information, for instance, for extracorporeal observation of blood pool in the heart and of cerebral and peripheral blood vessels and for determination of the volume of the whole blood circulation system. For development of such radioactive substances, a variety of investigations have been made in the field of nuclear medicine. .sup.131 I-Labeled human serum albumin (.sup.131 I-HSA) is now widely used for such purposes, but this labeled agent is not satisfactory because .sup.131 I has a long half life (i.e. about 8 days) and emits a .beta.-ray which gives a high radiation exposure to patients. In addition, its .gamma.-ray energy spectrum is not suitable for widely employed .gamma.-cameras for low energy.
Since technetium-99m (.sup.99m Tc) emits only a .gamma.-ray of about 140 KeV (not accompanied with .gamma.-ray) and has a short half life (i.e. about 6 hours), it is quite suitable as a radioactive nuclide for diagnostic agents to be administered to human bodies, and its utilization in the field of nuclear medicine has been rapidly increased in recent years.
Attempts have been made to label the blood circulation system with .sup.99m Tc in place of .sup.131 I-HSA, and the production of .sup.99m Tc-HSA and .sup.99m Tc-red blood cells by the extracorporeal labeling method have been proposed. However, .sup.99m Tc-HSA is inferior in labeling efficiency and stability in living bodies. .sup.99m Tc-red blood cells by the extracorporeal labeling method are also not satisfactory because of the complexity of a series of operations necessary for its production: i.e. collection of blood, separation of blood cells, addition of stannous compound, addition of pertechnetate (.sup.99m Tc), reaction, isolation and purification, and administration. In addition, there is a high possibility of bacterial contamination during the operations. Thus, the use of these labeling agents is not yet widely accepted.
On the other hand, intracorporeal labeling of red blood cells with .sup.99m Tc has been attempted by administering into a blood vessel an injectable liquid composition containing a stannous compound in the form of phosphate chelate and then administering a pertechnetate (.sup.99m TcO.sub.4.sup.-) so as to lael red blood cells with .sup.99m Tc specifically. This procedure of labeling has been attracting much interest because of its simplicity and high labeling efficiency, the high stability after labeling, etc. As the stannous phosphate chelate to be used in this procedure, there have been suggested stannous pyrophosphate (Sn-PPi), stannous ethane-1-hydroxy-1,1-diphosphonate (Sn-EHDP), stannous methylenediphosphonate (Sn-MDP), etc. Among them, Sn-PPi is employed most frequently.